SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT Synthamin 14, 8.5% Amino Acid Intravenous Infusion 2. QUALITATIVE AND QUANTITATIVE COMPOSITION L-Leucine Ph. Eur 0.620% w/v L-Isoleucine Ph. Eur 0.510% w/v L-Lysine (as hydrochloride salt) Ph. Eur 0.493% w/v L-Valine Ph. Eur 0.493% w/v L-Phenylalanine Ph. Eur 0.476% w/v L-Histidine Ph. Eur 0.408% w/v L-Threonine Ph. Eur 0.357% w/v L-Methionine Ph. Eur 0.340% w/v L-Tryptophan Ph. Eur 0.153% w/v L-Alanine Ph. Eur 1.760% w/v L-Arginine Ph. Eur 0.978% w/v Amino acetic acid (glycine) Ph. Eur 0.876% w/v L-Proline Ph. Eur 0.578% w/v L-Serine Ph. Eur 0.425% w/v L-Tyrosine Ph. Eur 0.034% w/v Sodium acetate Ph. Eur. 0.594% w/v Dibasic potassium phosphate Ph. Eur. 0.522% w/v Sodium chloride Ph. Eur. 0.154% w/v Magnesium chloride Ph. Eur. 0.102% w/v 3. PHARMACEUTICAL FORM The product is a sterile aqueous solution of amino acids and electrolytes for intravenous infusion to human beings. 4. CLINICAL PARTICULARS 4.1. Therapeutic indications Synthamin 14, 8.5% Amino Acid Intravenous Infusion provides a biologically available source of nitrogen (L-amino acids) for protein synthesis. When administered with an adequate source of energy such as concentrated carbohydrate solutions, minerals and vitamins, the mixture provides (with the exception of essential fatty acids) sufficient parenteral nutrition for patients unable to absorb adequate oral nutrition.
4.2. Posology and method of administration The solution is for administration by intravenous infusion through a central venous catheter with the tip located in the central vena cava. The total daily dose of the solution depends upon the patient s metabolic requirement and clinical response. The determination of nitrogen balance and accurate daily body weights, corrected for fluid balance, are probably the best means of assessing individual nitrogen requirements. In addition to meeting nitrogen needs, the rate of administration is governed, especially during the first few days of therapy, by the patient s ability to tolerate glucose. Daily intake of amino acids, electrolytes and glucose should be increased gradually to the maximum required dose as indicated by frequent determination of urine and blood sugar levels. Recommended daily dietary allowances for protein range from 2.2g/kg of body weight for infants to 56g of protein per day for adults weighing 70kg. An associated source of non-protein energy should be administered in a quantity not less than 0.75 megajoules (180kcal) per gram of nitrogen. In the initial treatment of severe trauma or in the presence of marked malnutrition, higher doses of amino acids with correspondingly larger quantities of carbohydrate will be necessary to promote adequate patient response to therapy. The degree of negative nitrogen balance being treated is the primary consideration in determining replacement therapy. In children, the dosage of parenteral nutrition should be individually tailored to the amino acid, electrolyte and energy requirements of the patient. 4.3. Contraindications Synthamin 14, 8.5% Amino Acid Intravenous Infusion is contraindicated in patients with renal failure, severe liver disease and patients with a known hypersensitivity to one or more amino acids. 4.4 Special warnings and precautions for use Hypersensitivity reactions and anaphylactic reactions have been reported with Synthamin. The infusion must be stopped immediately if any abnormal signs or symptoms of a hypersensitivity/anaphylactic reaction develop. Synthamin is hypertonic and may cause vein irritation in some patients. Frequent clinical evaluations and laboratory determinations are necessary for correct monitoring during administration. Studies should include blood sugar, serum proteins, kidney and liver function tests, electrolytes, haemogram, carbon dioxide combining power or content, serum and urine osmolarities, blood cultures and blood ammonia levels. Administration of amino acids solutions to a patient with hepatic insufficiency may result in serum amino acid imbalances, hyperammonaemia, stupor and coma. In infants, hyperammonaemia appears to be related to a defect in the ability to synthesise urea, and if amino acids are administered it is essential that blood ammonia is
measured frequently. Smaller doses of Synthamin should be administered to patients with known or suspected hepatic dysfunction. Should symptoms of hyperammonaemia develop, administration should be discontinued and the patient s clinical response re-evaluated. Mixtures containing amino acids may precipitate acute folate deficiency and folic acid should be administered daily. It is essential to provide an adequate source of non-protein energy concurrently if parenterally administered amino acids are to be retained by the body and utilised for protein synthesis. Concentrated glucose solutions are an effective source of such energy. The infusion of Synthamin with highly concentrated glucose solutions may result in hyperglycaemia, glycosuria and hyperosmolar syndrome. Blood and urine glucose should be monitored on a routine basis in patients receiving this treatment. Care should be taken to avoid circulatory overload particularly in patients with cardiac insufficiency. Do not administer unless the solution is clear and the container undamaged. Synthamin 2 litre and 3 litre presentations are bulk source containers for pharmacy use and should not be used for direct intravenous infusion. Label warning on 2 litre and 3 litre presentations: BULK SOURCE CONTAINER FOR PHARMACY USE NOT FOR DIRECT INTRAVENOUS INFUSION DO NOT STORE PARTLY USED CONTAINERS DISCARD ALL EQUIPMENT AFTER USE 4.5. Interaction with other medicaments and other forms of interaction None. 4.6. Fertility, pregnancy and lactation The safety of the use of Synthamin 14, 8.5% Amino Acid Intravenous Infusion during pregnancy or lactation has not been established. 4.7. Effects on ability to drive and use machines Not applicable. 4.8. Undesirable effects IMMUNE SYSTEM DISORDERS: Anaphylactic reactions (including shock), Hypersensitivity. The solution is hypertonic and liable to cause venous irritation at the site of injection.
4.9. Overdose None. 5. PHARMACOLOGICAL PROPERTIES 5.1. Pharmacodynamic properties None 5.2. Pharmacokinetic properties None 5.3. Preclinical safety data No data is presented as amino acids and electrolytes are basic and widespread elements in mammalian metabolism and therefore conventional animal safety testing is not appropriate. 6. PHARMACEUTICAL PARTICULARS 6.1. List of excipients Water for Injections Ph. Eur. QS to 100% Glacial Acetic Acid Ph. Eur. QS (for ph adjustment) Sodium Acetate Ph. Eur. QS (for ph adjustment) 6.2. Incompatibilities Synthamin 14, 8.5% Amino Acid Intravenous Infusion should not be administered simultaneously with, before or after an administration of blood through the same infusion equipment, because of the possibility of pseudo-agglutination. 6.3. Shelf life The shelf life is 24 months providing the unit has not been opened. 6.4. Special precautions for storage Storage temperature should not exceed 25 C. Product supplied in a clear overpouch should be protected from light during storage.
6.5. Nature and contents of container The products are supplied in PL-146 plastic (0.010 0.017 thickness) Viaflex containers which are sealed in a plastic laminated overpouch, or in dual bag containers sealed in a plastic laminated overpouch. The container is sealed with a closure made from PL-146 or from a blue-coloured plasticised PVC designated PL-141. The solutions are supplied in 250ml, 500ml, 1000ml, 2000ml and 3000ml fill volumes. 6.6. Special precautions for disposal and other handling 2 litre and 3 litre containers are bulk source containers for pharmacy use and should not be used for direct intravenous infusion. Discard any unused portion Do not reconnect partially used bag. Discard all equipment after use 7. MARKETING AUTHORISATION HOLDER Baxter Healthcare Ltd., Caxton Way, Thetford, Norfolk, IP24 3SE 8. MARKETING AUTHORISATION NUMBER PL 0116/0292 9. DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION 1 December 1997 / 7 September 2001 10. DATE OF REVISION OF THE TEXT 2 nd January 2014